The dopamine D2 and adenosine A2A receptors: past, present and future trends for the treatment of Parkinson's disease.

Herein, we present an overview of the historic development of drugs for the treatment of Parkinson's disease as well as prospective novel treatment forms based on targeting the dopamine and adenosine receptors. The review includes the development of levodopa, a precursor of the neurotransmitter dopamine, which to date is the most commonly prescribed and most effective drug for controlling the motor symptoms of Parkinson's disease, to more recent studies of the adenosine receptor; a promising target for the treatment of Parkinson's disease due to its intrinsic neuroprotective nature. Ongoing and future drug-based research on the dopamine and adenosine receptors has the advantage of being guided by the improved understanding of receptor topography as well as their functional roles. Breakthroughs such as the first ligand-bound X-ray structure of a selective adenosine A2A receptor antagonist in complex with the adenosine A2A receptor, the discovery of the existence of dopamine D2 homodimers, dopamine D2- adenosine A2A heterodimers and higher order oligomers in addition to technological progress have changed the direction of research in academia and industry and form the pillars for novel and exciting discoveries in this field.